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    Spatial and temporal diversity in genomic instability processes defines lung cancer evolution

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    SpatialTemporal.pdf (1.467Mb)
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    URI: http://hdl.handle.net/10902/9726
    ISSN: 0036-8075
    ISSN: 1095-9203
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    Author
    Bruin, Elza C de; McGranahan, Nicholas; Mitter, Richard; Salm, Max; Wedge, David C; Yates, Lucy; Jamal-Hanjani, Mariam; Horswell, Stuart; Gerlinger, Marco; Varela Egocheaga, IgnacioAutoridad Unican; Jones, David; Marshall, John; Voet, Thierry; Loo, Peter van; Rassl, Doris M; Rintoul, Robert C; Janes, Sam M; Lee, Siow-Ming; Foster, Martin; [et al.]
    Date
    2014
    Publicado en
    Science. 2014 Oct 10;346(6206):251-6
    Enlace a la publicación
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636050/pdf/emss-65871.pdf
    Abstract:
    Spatial and temporal dissection of the genomic changes occurring during the evolution of human non-small cell lung cancer (NSCLC) may help elucidate the basis for its dismal prognosis. We sequenced 25 spatially distinct regions from seven operable NSCLCs and found evidence of branched evolution, with driver mutations arising before and after subclonal diversification. There was pronounced intratumor heterogeneity in copy number alterations, translocations, and mutations associated with APOBEC cytidine deaminase activity. Despite maintained carcinogen exposure, tumors from smokers showed a relative decrease in smoking-related mutations over time, accompanied by an increase in APOBEC-associated mutations. In tumors from former smokers, genome-doubling occurred within a smoking-signature context before subclonal diversification, which suggested that a long period of tumor latency had preceded clinical detection. The regionally separated driver mutations, coupled with the relentless and heterogeneous nature of the genome instability processes, are likely to confound treatment success in NSCLC.
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    UNIVERSIDAD DE CANTABRIA

    Repositorio realizado por la Biblioteca Universitaria utilizando DSpace software
    Contact Us | Send Feedback
    Metadatos sujetos a:licencia de Creative Commons Reconocimiento 3.0 España